The risk is not huge. But the drugs work so well and so safely — and are advertised so aggressively — that they're among the most-used drugs in the U.S. With so many users, any risk would involve lots of people.
There seems to be one extra case of pneumonia among every 100 people who take acid-suppressing drugs for one year. The finding comes from researchers Robert J.F. Laheij, PhD, of the University Medical Center St. Radboud in Nijmegen, Netherlands. Laheij and colleagues report their findings in the Oct. 27 issue of The Journal of the American Medical Association.
"These drugs are not as safe as everybody thinks," Laheij tells WebMD. "If it is not necessary for you to use them, don't. Keep in mind that these medicines can have serious side effects — especially in more fragile patients who can have serious problems."
The researchers analyzed computerized medical records for some 500,000 Dutch patients. Those taking acid-suppressing drugs for heartburn and indigestion were four times more likely to have pneumonia than those who did not.
Since people taking these drugs tend to be less healthy, the researchers did a second, more meaningful analysis. They compared those still taking the drugs with those who used to take them but stopped. Current use of acid-suppressing drugs doubled the risk of pneumonia.
Who Needs Acid-Suppressing Drugs
The drugs in question are called proton pump inhibitors (search) or PPIs. They block the chemical "pump" needed for stomach cells to make acid. The drugs include:
Prilosec (called Losec in Europe); Nexium; Prevacid; Protonix; Aciphex
Also implicated in pneumonia risk to a lesser extent are the acid-fighting drugs called H2 receptor antagonists (search). They block a different step in the manufacture of stomach acid. These drugs include:
Tagamet; Pepcid; Axid; Zantac; Rotane
Acid-suppressing drugs work wonders for people who really need them, says David Peura, MD. Peura is spokesman for the American Gastroenterological Association and associate chief of gastroenterology at the University of Virginia in Charlottesville.
"PPIs are appropriate for people who truly have GERD [acid reflux], where their symptoms are affecting their quality of life," Peura tells WebMD. "These are people who have difficulty sleeping, who are altering their lifestyles for the better and still are not able to control their symptoms. Most of these people have serious heartburn three or more times a week."
The H2 antagonists are "ideally suited" for people with only occasional heartburn, Peura says. Most people need these drugs only once in a while.
"If you were going to eat a pizza and thought you would have a problem, you'd be better off taking Zantac or Pepcid before going out instead of taking the drugs on a regular basis," Peura says. "But there are others who when they just bend over, acid comes up into their esophagus. These people need regular acid suppression."
Lifestyle changes can reduce the risks of heartburn, such as:
—Avoid foods and beverages that contribute to heartburn: chocolate, coffee, peppermint, greasy or spicy foods, tomato products, and alcoholic beverages
—Do not lie down after eating
How Acid-Suppressing Drugs Promote Infection
How might these drugs cause infection? Exactly the same way they work: by suppressing stomach acid. While it sounds bad, stomach acid is the body's first line of defense against swallowed germs. The acid can kill bacteria and viruses that cause pneumonia.
The bodies of healthy people have plenty of other ways to fight germs. But elderly people and those with chronic diseases need all the germ-fighting help they can get. This is exactly who is at most risk for pneumonia when using acid-suppressing drugs.
Laheij's team found the risk of severe pneumonia to be highest in the elderly. Children and people with weakened or suppressed immune systems were also at higher risk. And there was a greater risk of pneumonia in users of acid-suppressing drugs who had asthma or lung disease.
It's not clear how germs from the stomach get into the lungs to cause pneumonia. But the new link to pneumonia means doctors will keep a closer eye on patients who take acid-suppressing drugs, says lung specialist Greg Martin, MD, MSc. Martin teaches pulmonary, allergy, and critical care medicine at Emory University and is director of the pulmonary clinic and the medical intensive care unit at Grady Memorial Hospital in Atlanta.
"Now doctors need to think differently about lung infections," Martin tells WebMD. "What we will do now, maybe we'll be telling people taking PPIs to take mild pneumonia symptoms more seriously. Now you say to a patient, 'Well, the fever is not that high, you are not short of breath, it is nothing major; go home and take a day off, see if you feel better.' Now, in the context of this study, if a person is taking these drugs, maybe we should be taking an X-ray to make sure they don't have pneumonia."
If you're taking acid-suppressing drugs, Martin says, it's a good idea to know the early symptoms of pneumonia:
—Fever, usually over 100.5 degrees and up
—Cough, especially a wet cough with phlegm production
—Chest pain, especially on one side, that is made worse with deep breathing
—Shortness of breath without exertion
"Fever should go with some other symptoms," Martin says. "The real pneumonia symptoms we think of are fever and cough. Shortness of breath can be another symptom, but it is not always there. And shortness of breath can have a lot of causes, so it's not an indicator of pneumonia all by itself."
Chest pain, Martin notes, can also be a sign of the kinds of stomach problems treated with acid-suppressing drugs. So can a cough, notes gastroenterologist Peura. In fact, Peura says, it's no secret that people with untreated reflux disease are at increased risk of pneumonia.
"How much more pneumonia would the patients in the Laheij study have had if they not been treated?" Peura asks. "Severe reflux can be associated with pneumonia. ... Yes, those at highest risk of pneumonia appeared to be those taking the highest doses [of acid-suppressing drugs]. But maybe that is because their reflux was more severe. Was it reflux causing the pneumonia — in which case acid suppression with a PPI was the appropriate treatment — or was acid suppression putting people at risk for pneumonia?"
Though the Laheij study strongly suggests a link between regular use of acid-suppressing drugs and pneumonia, it does not offer definitive proof. Still, all of the experts who spoke with WebMD urge people to take the drugs only as needed.
In an editorial accompanying the Laheij study, James C. Gregor, MD, warns that even the safest-seeming drugs can have serious side effects.
"These acid-suppressing drugs have an incredible track record of safety. In fact, of almost every bad thing people said could happen when these drugs first were developed, virtually none have happened," Gregor tells WebMD. "These drugs are very useful in the right situation, not only to improve symptoms but to heal disease and to prevent complications. But when used inappropriately, in the wrong situation — such as a replacement for a healthier lifestyle — people may be subjecting themselves to risk with no known benefit."
Gregor says many doctors are prescribing nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, Motrin, and Aleve, to relieve arthritis pain. But because these drugs have a small risk of causing stomach ulcers, doctors are prescribing acid-suppressing drugs with them.
"The risk of pneumonia from a PPI is almost identical to the risk of bleeding from an NSAID," Gregor says. "We will probably in the next few months see people switched to chronic PPI use to protect them from NSAID bleeding. Maybe we'll be trading the risk of a bleed for risk of pneumonia."
SOURCES: Laheij, R.J.F. The Journal of the American Medical Association, Oct. 27, 2004; vol 292: pp 1955-1960. Gregor, J.C. The Journal of the American Medical Association, Oct. 27, 2004; vol 292: pp 2012-2013. Robert J.F. Laheij, PhD, University Medical Center St. Radboud, Nijmegen, Netherlands. James Gregor, MD, director for gastroenterology and associate chairman of medicine, University of Western Ontario, London, Ontario. David Peura, MD, spokesman, American Gastroenterological Association; associate chief of gastroenterology, University of Virginia, Charlottesville. Greg Martin, MD, MSc, assistant professor, division of pulmonary, allergy, and critical care medicine, Emory University School of Medicine; director, pulmonary clinic and medical intensive care unit, Grady Memorial Hospital, Atlanta.